Pulmonary fibrosis (which is also called interstitial lung disease) refers to a disease that produces scar-like tissue in pulmonary interstices by accumulating extracellular matrix (ECM) components such as collagen, elastin and fibronectin in pulmonary interstitial tissue. Pulmonary fibrosis makes pulmonary tissue, which is originally as soft as a sponge, becomes as hard as concrete and thus loses elasticity, resulting in a gradually loss of the capabilities to contract, relax and exchange gas.
Generally, patients at an early stage of pulmonary fibrosis will have symptoms such as hyperpnoea, chest tightness and pain, cough, etc. However, those early stage symptoms are not easy to identify. Therefore, more than 50% of the pulmonary fibrosis patients have been misdiagnosed with asthma, emphysema, chronic obstructive pulmonary disease (COPD), or heart diseases. When definitely diagnosed, most of the pulmonary fibrosis patients' pulmonary functions have already decreased, and those patients also have the symptom of dyspnea, leading to chronic hypoxia. When the body lacks oxygen, attention and memory will decrease, and in addition, insufficient oxygen lead to cell weakness, physical function decline, slow metabolism, increased aging, various complications, etc. As for patients with late-stage pulmonary fibrosis, they can have heart failure and respiratory failure caused by long-term hypoxia, and even need to depend on inhaling air with a high concentration of oxygen to maintain life when the disease becomes severe.
The mortality rate of the pulmonary fibrosis patients is much higher than that of cancer patients. According to statistics, patients with pulmonary fibrosis have a five-year survival rate less than 50%, and a ten-year survival rate less than 10%. There is still a lack of medicaments that can effectively treat pulmonary fibrosis. The commercially available medicament, Pirfenidone (product name: Esbriet®), can improve the lung capacity of pulmonary fibrosis patients, but it does not have significant benefits on treating pulmonary fibrosis. Besides, Pirfenidone may produce various side-effects, such as nausea, emesis, dyspepsia, anorexia, erythematous rash, dizziness, photosensitivity, etc. Therefore, in clinic practice, there is still a need of a medicament that can delay the onset of pulmonary fibrosis and/or treat pulmonary fibrosis.
The inventors of the present invention found that the compound of formula (I) has the effects of enhancing the anti-oxidation capability of alveolar cells, increasing the survival rate of alveolar cells, alleviating oxidative stress-induced injury to the pulmonary tissue, inhibiting pulmonary fibroblast to myofibroblast conversion, inhibiting the epithelial-mesenchymal transition (EMT) of pulmonary fibroblasts and inhibiting the overexpression of extracellular matrix. Moreover, the compound of formula (I) can effectively regulate the immune response in pulmonary tissue, alleviate the thickening of alveolar wall tissue, alleviate the abnormal infiltration of pulmonary cells and/or alleviate the decrease in pulmonary function; thus it can be used to delay the onset of pulmonary fibrosis and/or treat pulmonary fibrosis.